类风湿关节炎血浆外泌体中 microRNA 谱的特征及其在 B 细胞反应中的作用。

Characterization of the MicroRNA profile in rheumatoid arthritis plasma exosomes and their roles in B-cell responses.

机构信息

Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.

Department of Laboratory Medicine, the Affiliated Guangji Hospital of Soochow University, Suzhou Mental Health Center, Suzhou, Jiangsu, China.

出版信息

Clinics (Sao Paulo). 2024 Jul 7;79:100441. doi: 10.1016/j.clinsp.2024.100441. eCollection 2024.

DOI:10.1016/j.clinsp.2024.100441

PMID:38976936

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11294701/

Abstract

OBJECTIVE

This study aimed to identify differentially expressed microRNAs (miRNAs) in exosomes derived from the blood plasma of Rheumatoid Arthritis (RA) patients and explore their clinical significance and biological roles.

METHODS

Illumina high-throughput sequencing was employed to measure miRNA expression levels in plasma exosomes, followed by validation using qRT-PCR. The correlation between exosomal miRNAs and disease activity was systematically analyzed. Additionally, the pathogenic effects of RA exosomes were investigated through bioinformatics analysis and in vitro experiments.

RESULTS

Significantly reduced levels of exosomal miR-144-3p and miR-30b-5p were observed in RA patients, which were negatively correlated with DAS28 scores and anti-CCP antibody levels. ROC curve analysis showed that miR-144-3p and miR-30b-5p in plasma exosomes could effectively distinguish RA patients from healthy controls, with AUC values of 0.725 and 0.773, respectively. Combining bioinformatics analysis and in vitro experiments, it was demonstrated that plasma exosomes contribute to ongoing autoantibody production in RA by promoting B-cell differentiation and antibody production.

CONCLUSION

The present study indicates that plasma exosomes from RA patients may be potentially pathogenic. Exosomal miR-144-3p and miR-30b-5p exhibit significant decreases in RA patients and are associated with disease activity, suggesting their potential as valuable biomarkers for RA.

摘要

目的

本研究旨在鉴定类风湿关节炎（RA）患者血浆来源的外泌体中差异表达的 microRNAs（miRNAs），并探讨其临床意义和生物学作用。

方法

采用 Illumina 高通量测序测量血浆外泌体中的 miRNA 表达水平，并用 qRT-PCR 进行验证。系统分析外泌体 miRNAs 与疾病活动度的相关性。此外，通过生物信息学分析和体外实验研究 RA 外泌体的致病作用。

结果

RA 患者的外泌体 miR-144-3p 和 miR-30b-5p 水平显著降低，与 DAS28 评分和抗 CCP 抗体水平呈负相关。ROC 曲线分析表明，血浆外泌体中的 miR-144-3p 和 miR-30b-5p 能够有效地区分 RA 患者与健康对照者，AUC 值分别为 0.725 和 0.773。结合生物信息学分析和体外实验，表明血浆外泌体通过促进 B 细胞分化和抗体产生，有助于 RA 中持续的自身抗体产生。